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MK ACVD Exam > Epidermis, cornification, keratinization > Flashcards

Epidermis, cornification, keratinization Flashcards

1
Q

What keratins are expressed by basal keratinocytes in dogs?

A

K5, K14, K1, K6 (5+14 are the main ones to know)

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2
Q

How many cells are included in the epidermal proliferative unit model of epidermal stem cell division?

A

10 cells (in basal layer)

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3
Q

What population of cells is unique to the epidermal proliferative unit?

A

Transit amplifying cells - these proliferate rapidly to produce terminally differentiating cells in the epidermis

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4
Q

Name the layers of the epidermis (deep to superficial)

A

Basale - spinosum - granulosum - corneum

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5
Q

What makes up the spines of the cells in the stratum spinosum?

A

Desmosomes

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6
Q

What proteins and keratins start to be produced in the spinous cell layer?

A

K1, K10, involucrin, profilaggrin

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7
Q

What are keratohyalin granules?

A

Accumulations of synthesized proteins and lipids needed for the SC (primarily profilaggrin, loricrin, KIF)

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8
Q

In what layer of the epidermis do the KIF begin to assemble?

A

Stratum granulosum

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9
Q

In what layer does construction of the cornified envelope begin?

A

Stratum granulosum

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10
Q

Where are the contents of lamellar granules released?

A

Interface between stratum granulosum and stratum corneum

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11
Q

What does the cornified cell envelope take the place of?

A

Plasma membrane

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12
Q

What type of filament of the epithelial cell cytoskeleton is the largest?

A

Microtubules (20 nm diameter)

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13
Q

What type of filament of the epithelial cell cytoskeleton is the smallest?

A

Microfilaments (7 nm diameter, composed of actin)

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14
Q

Describe the structure of keratin proteins

A

Central alpha-helical rod domain, amino-terminal head, and carboxy-terminal tail

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15
Q

What type of keratins are acidic?

A

Type I (K9-19)

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16
Q

What type of keratins are basic or neutral?

A

Type II (K1-8)

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17
Q

What protein binds KIFs, facilitating the flattening of cornified cells?

A

Filaggrin

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18
Q

What is the general term for filaggrin degradation products?

A

Natural moisturizing factors

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19
Q

What are the products of filaggrin degradation?

A

AAs
urocanic acid
pyrrolidone carboxylic acid
lactic acid
citrate
sugars

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20
Q

What enzyme is required for filaggrin degradation?

A

Caspase-14

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21
Q

An increase in which intracellular ion results in increased transglutaminase activity?

A

Calcium

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22
Q

What enzymes catalyze the formation of bonds which cross-link involucrin to other CE proteins?

A

Transglutaminases 1+3

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23
Q

What protein is the major structural component of the cornified envelope?

A

Loricrin (70% of CE mass)

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24
Q

What enzyme cross-links loricrin to small proline-rich peptides?

A

Transglutaminase 3

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25
Q

What enzyme cross-links the loricrin+proline-rich peptide oligomers to the CE?

A

Transglutaminase 1

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26
Q

What protein helps traffic lamellar granules from the Golgi network to the plasma membrane?

A

CHEVI complex
(C-homologues in endosome-vesicle interaction)

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27
Q

What is the primary signal that induces lamellar granule secretion between the granular and cornified layers?

A

Increased intracellular calcium

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28
Q

What converts glucosylceramides into ceramides in the intercellular lamellae?

A

beta-glucocerebrosidase

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29
Q

What are the breakdown products of phospholipids?

A

FFAs, glycerol

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30
Q

What is the function of glycerol in the SC?

A

hydration (hygroscopic molecule)

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31
Q

What is the function of FFAs in the SC?

A

acidification – important for enzyme functions (esp beta-glucocerebrosidase and acidic sphingomyelinase)

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32
Q

What is the breakdown product of sphingomyelin?

A

ceramides

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33
Q

What enzyme converts sphingomyelin into ceramides?

A

acidic sphingomyelinase

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34
Q

What are the major lipid classes in the SC?

A

ceramides (50% of lipid mass)
FFAs (25% of lipid mass)
cholesterol (15% of lipid mass)

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35
Q

What group of ceramides is unique to the SC?

A

omega-hydroxyceramides (ceramides 1, 4, 9)

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36
Q

What are omega-hydroxyceramides bonded to?

A

involucrin, envoplakin, periplakin (help make up the cornified lipid envelope)

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37
Q

What would be the clinical manifestation of a malformation of the cornified lipid envelope?

A

Ichthyosis

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38
Q

What two enzymes are the key rate limiting enzymes in FFA synthesis?

A

acetyl-CoA carboxylase, fatty acid synthase

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39
Q

What fatty acids are NOT synthesized by the epidermis?

A

omega-3+6 polyunsaturated EFAs (i.e. linoleic acid and alpha-linolenic acid)

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40
Q

What specific fatty acids must be supplied by the diet/topicals?

A

linoleic acid (omega 6 PUFA)
alpha-linolenic acid (omega 3 PUFA)

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41
Q

What is the rate-limiting enzyme in cholesterol synthesis?

A

hydroxymethylglutaryl CoA reductase (HMG CoA)

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42
Q

What are two possible outcomes that happen to cholesterol synthesized in the lower epidermis?

A

1) Some is incorporated into lamellar granules and secreted into SG-SC interface unchanged
2) Some is sulfurylated, diffuses across membrane, and is metabolized back to cholesterol

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43
Q

What enzyme converts cholesterol sulfate back to cholesterol

A

Steroid sulfatase

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44
Q

Where does steroid sulfatase come from?

A

Secreted by lamellar granules

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45
Q

What is the role of cholesterol sulfate?

A

Inhibits serine proteases involved in desquamation

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46
Q

What is the desmoglea?

A

Extracellular part of desmosomes between adhered keratinocytes

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47
Q

Which desmosome plaque is intertwined with KIFs?

A

Inner dense plaque

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48
Q

What desmosome plaque borders the plasma membrane?

A

Outer dense plaque

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49
Q

What proteins are the transmembrane molecules that form an adhesive interface between neighboring keratinocytes?

A

Cadherins

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50
Q

What cadherins comprise the desmoglea?

A

Desmogleins
Desmocollins

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51
Q

What protein family binds to the cytoplasmic portion of cadherins?

A

Armadillo proteins (Plakoglobin, plakophilin)

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52
Q

What protein binds desmoplakin and cadherins?

A

Plakoglobin

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53
Q

What protein facilitates lateral linkage between desmoplakins?

A

Plakophilin

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54
Q

What protein binds KIFs to plakoglobin?

A

Desmoplakin

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55
Q

What do corneodesmosomes contain?

A

Desmoglein 1, desmocollin 1, corneodesmosin

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56
Q

What proteins in the epidermis are known to have glycine loops?

A

Keratins, loricrin, corneodesmosin

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57
Q

What is the function of glycine loops?

A

Mediate reversible and adjustable adhesion (acts like Velcro not glue)

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58
Q

Where is corneodesmosin synthesized?

A

In the granular keratinocyte

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59
Q

Where is corneodesmosin secreted?

A

Into the intercellular space starting in the SECOND layer of the SG

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60
Q

What protein is progressively cleaved as corneocytes advance towards desquamation?

A

Corneodesmosin

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61
Q

How does corneodesmosome distribution differ between lower and upper SC?

A

Lower SC: corneodesmosomes are all around the KC surface
Superficial SC: corneodesmosomes are only at periphery of KC

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62
Q

What is responsible for the superficial basket-weave of the layers of the upper SC?

A

Corneodesmosome distribution limited to periphery of cells in the upper SC
(deeper SC appears more compact microscopically because corneodesmosomes are all around the KC)

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63
Q

What transmembrane molecules make up epidermal tight junctions?

A

Claudins
Occludins

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64
Q

Which claudins are expressed in the epidermis?

A

Claudins 1, 4, 7

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65
Q

Which intracellular proteins help make up epidermal tight junctions?

A

zonula occludens proteins

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66
Q

Where are adherens junctions found on basal cells?

A

Lateral and apical membranes

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67
Q

Where are adherens junctions found on suprabasal cells?

A

entire cell surface

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68
Q

What junction links the actin cytoskeleton to the plasma membrane?

A

Adherens junctions

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69
Q

What protein classes are involved in adherens junctions?

A

Cadherins and catenins

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70
Q

How long does it take for complete renewal of the human epidermis?

A

28 days

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71
Q

What 2 protein classes are involved in desquamation?

A

kallikreins
Cathepsins

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72
Q

What proteins are cleaved by KLK5?

A

Corneodesmosin
Desmoglein 1
Desmocollin 1

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73
Q

What proteins are cleaved by KLK7?

A

Corneodesmosin
Desmocollin 1

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74
Q

Which KLK are involved in degrading corneodesmosomes?

A

KLK 1, 5, 6, 7, 14

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75
Q

Which KLK degrade desmoglein 1?

A

KLK 1, 5, 6, 14

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76
Q

What proteins cleave corneodesmosin?

A

KLK 5
Cathepsin L-like enzyme
Cathepsin D

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77
Q

What is the concentration of Ca2+ in the lower epidermis as compared to the upper epidermis?

A

Low in SB and SS, increased in SG, decreased again in SC

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78
Q

What structures provide a barrier to water loss in non-cornified epidermis?

A

Tight junctions

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79
Q

What structures regulate the Ca2+ gradient in the epidermis?

A

Tight junctions and the SC

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80
Q

What proteins provide most of the mechanical protection of the epidermis?

A

Keratins, filaggrin

81
Q

What is the primary barrier to movement of electrolytes and water in the SC?

A

Extracellular lipid matrix (cholesterol, FFAs, ceramides)

82
Q

What parts of the SC provide protection from UV radiation?

A

Byproducts of filaggrin metabolism

83
Q

Describe the structure of phospholipids

A

Glycerol (head) + phosphate group (head) + 2 FAs (tail)

84
Q

What is the optimal water concentration of the SC?

A

20-35%

85
Q

Between which epidermal layers is the stratum lucidum found?

A

Between SC and SG

86
Q

Is TEWL increased or decreased in dogs with atopy?

A

Increased

87
Q

How do skin lipids in dogs and cats differ from humans?

A

Dogs and cats have more sterol esters, free cholesterol, and diester waxes

88
Q

Describe the structure of a ceramide

A

FA linked to a sphingoid base

89
Q

What protein helps incorporate glucosylceramide into lamellar granules?

A

ABCA12

90
Q

What is the most abundant lipid in the body?

A

Cholesterol

91
Q

What is the most abundant lipid in the SC?

A

Ceramides

92
Q

Describe the structure of FFAs

A

Long carbon chain with a methyl group at one end

93
Q

What protein is key in the uptake of FAs into keratinocytes?

A

Fatty acid transport protein (FATP4)

94
Q

What type of lipid incorporates FFAs?

A

Ceramides

95
Q

What food contains high levels of linoleic acid?

A

Plants

96
Q

What are the essential fatty acids in cats?

A

Arachidonic acid linoleic acid

97
Q

What food contains high levels of a-linolenic acid?

A

Fish

98
Q

What are the metabolites of alpha-linolenic acid?

A

EPA, DHA

99
Q

What type of fatty acids are anti-inflammatory?

A

Omega-3

100
Q

What type of fatty acids are pro-inflammatory?

A

Omega-6

101
Q

What are the essential fatty acids in dogs?

A

Linoleic acid, alpha-linolenic acid

102
Q

What enzyme allows for free arachidonic acid to be released from the phospholipid membrane into the skin?

A

Phospholipase A2 (PLA2)

103
Q

What enzyme is mutated in Harlequin ichthyosis?

A

ABCA12 (important for transfer of glucosylceramides into lamellar bodies)

104
Q

What lipid changes occur between the SG and SC?

A

Phospholipids replaced by ceramides
Increase in free sterols
Increase in FFAs, decrease in triglycerides and phospholipids

105
Q

What is the effect of increased pH on desquamation?

A

Increased protease activity –> increased desquamation

106
Q

What is the pathogenesis of epidermolytic ichthyosis?

A

Defect in keratin formation

107
Q

What is the mode of inheritance of ichthyosis in Norfolk Terriers?

A

Autosomal recessive

108
Q

What breeds are predisposed to epidermolytic ichthyosis?

A

Norfolk Terriers, Rhodesian Ridgebacks, Labs

109
Q

What gene is mutated in epidermolytic ichthyosis in Labs and Rhodesian Ridgebacks?

A

NSDHL

110
Q

What is the pathogenesis of non-epidermolytic ichthyosis?

A

Defect in formation of lipid layer or cornified envelope

111
Q

What gene is mutated in ichthyosis in Norfolk Terriers?

A

KRT10

112
Q

What genes are mutated in ichthyosis in Golden Retrievers?

A

PNPLA1 (needed for CLE formation)
ABHD5

113
Q

What gene is mutated in ichthyosis of American Bulldogs?

A

NIPAL-4 (cofactor for FATP4)

114
Q

What gene is mutated in ichthyosis in JRTs?

A

Transglutaminase-1 (mediates Ca2+ dependent cross-linking of involucrin and loricrin to form cornified envelope)

115
Q

What gene is mutated in ichthyosis in Great Danes?

A

SLC27A4 (encodes FATP4 synthesis)

116
Q

What gene is mutated in ichthyosis in GSDs?

A

ASPRV1 (profilaggrin-filaggrin processing)

117
Q

What breeds are predisposed to ARCI (autosomal recessive congenital ichthyosis)?

A

CKCS, Golden Retriever, JRT, Great Dane, American Bulldog

118
Q

What form of ichthyosis in cattle is lethal?

A

Ichthyosis fetalis (bovine harlequin ichthyosis)

119
Q

What cattle breeds are predisposed to Harlequin ichthyosis?

A

Chianina
Holstein-Friesian
Brown Swiss
Norwegian Red Poll
Hanwoo
Polled Hereford
Shorthorn
Belgian White and Red

120
Q

What form of ichthyosis in cattle is mild?

A

Ichthyosis congenita

121
Q

What breeds are predisposed to ichthyosis congenita in cattle?

A

Jersey
Pinzgauer
Holstein-Friesian
Chianina

122
Q

What lipid is substituted into the phospholipid membrane in seborrhea?

A

Oleic acid (less flexible than linoleic acid)

123
Q

What is the thickness (mm) of normal canine skin?

A

0.1-0.5 mm

124
Q

Where might you find rete ridges in canine skin?

A

Footpads, nasal planum, scrotum

125
Q

Where on the body is the stratum spinosum thickest?

A

Feet, nasal planum, MC junctions

126
Q

Is the SG thicker in haired or non-haired skin?

A

Non-haired (4-8 cell layers thick)

127
Q

Where is the stratum lucidum found?

A

Footpads and nasal planum only

128
Q

What is the only epidermal layer that contains desmoglein 3?

A

Stratum spinosum

129
Q

What cadherins are found in all layers of the epidermis?

A

Desmocollin-2
Desmocollin-3
E-cadherin

130
Q

What cadherins are found only in the stratum basale?

A

Desmoglein-2
P-cadherin

131
Q

What cadherins are in all layers of the epidermis EXCEPT the stratum basale?

A

Desmoglein-1
Desmoglein-4
Desmocollin-1

132
Q

What is the primary scaffold protein of the cornified envelope?

A

Involucrin

133
Q

What proteins makes up 80-90% of the epidermal mass?

A

Filaggin and keratin

134
Q

What are the 4 distinct cellular events in cornification?

A

1) Keratinization
2) Keratohyalin synthesis
3) CE formation
4) Lamellar body synthesis

135
Q

Where is K2 expressed?

A

Stratum granulosum

136
Q

What is the molecular target in pemphigus vulgaris?

A

Desmoglein-3

137
Q

What is the molecular target in lamellar ichthyosis?

A

transglutaminase-1

138
Q

What is the molecular target in ectodermal dysplasia?

A

Plakophilin-1

139
Q

What is the epidermal turnover rate in seborrheic Cocker Spaniels?

A

7 days

140
Q

What is the epidermal turnover rate in normal canine skin?

A

22 days

141
Q

What is the epidermal turnover rate in normal bovine skin?

A

18 days

142
Q

What is the epidermal turnover rate in normal murine skin?

A

8-10 days

143
Q

What is the molecular target in human PF?

A

Desmoglein-1

144
Q

What is the molecular target in canine PF?

A

Desmocollin-1

145
Q

What cell layer contains mitotic cells?

A

S. basale (other layers do not)

146
Q

What layer of the epidermis contains tight junctions?

A

S. granulosum

147
Q

What filaggrin breakdown product offers some UV protection?

A

Urocanic acid

148
Q

A defect in which protein in cornification is known to be a major predisposing factor for the development of AD in humans?

A

Filaggrin

149
Q

Where would a keratin 10 mutation most likely manifest in the epidermis?

A

Stratum spinosum/stratum granulosum

150
Q

At which pH are kallikreins active?

A

Neutral

151
Q

What is demonstrated on the right side of the photo below as compared to the left side?

A

Right side demonstrates ichthyosis: irregular arrangement of enlarged corneocytes with entombed lamellar body contents (arrowheads)

152
Q

What is the mode of inheritance of ichthyosis in Labs?

A

X-linked semidominant

153
Q

In which breed does ichthyosis result in non-viability shortly after birth?

A

Great Danes

154
Q

What structure is attenuated or absent in both Golden Retriever and American Bulldog ichthyosis?

A

Cornified lipid envelope

155
Q

What organism is likely to overgrow in ichthyosis?

A

Malassezia

156
Q

What structure is lost or attenuated in ichthyosis in JRTs?

A

Cornified envelope (NOT the cornified lipid envelope)

157
Q

What are the clinical signs of ichthyosis in CKCS?

A

KCS, rough curly coat, nail dystrophy, scaling

158
Q

What is the mutation in paw pad hyperkeratosis in the dogues de Bordeaux?

A

KRT16

159
Q

What is the mutation in paw pad hyperkeratosis in Irish terriers and Kronfohrlanders?

A

FAM83G

160
Q

What is the mutation in hereditary nasal parakeratosis in Labs?

A

SUV39H2 (decreases expression of loricrin in the SC)

161
Q

What is the primary function of bleomycin hydrolase and caspase 14?

A

degradation of intracellular filaggrin into free AAs

162
Q

What occurs in the initiation phase of CE formation?

A

synthesis of CE structural proteins

163
Q

What occurs in the reinforcement phase of CE formation?

A

attachment of lipids to CE proteins

164
Q

What enzyme is essential to inhibit kallikreins in the intercellular space to prevent early desquamation?

A

LEKTI

165
Q

Is sulfur keratolytic or keratoplastic?

A

Both

166
Q

Is tar keratolytic or keratoplastic?

A

Both

167
Q

Is benzoyl peroxide keratolytic or keratoplastic?

A

Keratolytic

168
Q

Is selenium sulfide keratolytic or keratoplastic?

A

Both (and degreasing)

169
Q

What is the typical age of onset of primary seborrhea?

A

12-18 months (though as early as 10 weeks)

170
Q

What feline breed is predisposed to ulcerative nasal dermatitis?

A

Bengals

171
Q

What is the average epidermal renewal time in cases of ichthyosis?

A

~3.6 days

172
Q

What is the typical age of onset of ichthyosis in Golden Retrievers?

A

<1 year (though adult onset is reported)

173
Q

Which breed has a form of ichthyosis that is homologous with lamellar ichthyosis in humans?

A

JRTs (TGM1 deficiency)

174
Q

What gene is mutated in canine X-liked cornification defects and causes CHILD syndrome in people?

A

NSDHL (codes for a protein involved in cholesterol synthesis)

175
Q

What is the typical distribution of X-linked cornification defect/CHILD syndrome on the skin?

A

Along Blaschko’s lines

176
Q

What breeds are predisposed to vitamin A-responsive dermatosis?

A

American Cocker Spaniels
Labs
Miniature Schnauzers
Gordon Setters

177
Q

How should oral vitamin A be administered?

A

With a fatty meal

178
Q

What is the proposed pathogenesis of psoriasiform-lichenoid dermatosis?

A

exaggerated reaction to Staph infection

179
Q

Which breed is predisposed to psoriasiform-lichenoid dermatosis?

A

English Springer Spaniels

180
Q

What dermal cell infiltrate is a main feature of psoriasiform-lichenoid dermatitis?

A

Plasma cells
(neutrophilic and eosinophilic microaggregates also present)

181
Q

What are the clinical signs of Schnauzer comedo syndrome?

A

Non-painful, non-pruritic comedones on dorsal midlines between shoulders and sacrum

182
Q

What mutation has been identified in footpad hyperkeratosis in Rottweilers?

A

DSG1 frameshift mutation

183
Q

What breeds are predisposed to hereditary nasal hyperkeratosis?

A

Labs, Greyhounds

184
Q

What is the mode of inheritance for sebaceous adenitis?

A

autosomal recessive

185
Q

What cytokines are elevated in the skin during inflammation and would stimulate epidermal proliferation, leading to secondary seborrhea?

A

leukotriene B4, PGE2

186
Q

What type of zinc-responsive dermatosis is more common in Arctic breed dogs?

A

Syndrome 1

187
Q

What breed are predisposed to zinc-responsive dermatosis syndrome 2?

A

Rapidly growing large breeds

188
Q

What can exacerbate zinc-responsive dermatosis?

A

Estrus (estrogen competes with zinc for serum proteins)

189
Q

What is the gene mutation in lethal acrodermatitis of white bull terriers?

A

MKLN1

190
Q

What is the mode of inheritance of lethal acrodermatitis?

A

Autosomal recessive

191
Q

Does lethal acrodermatitis respond to zinc supplementation?

A

No

192
Q

What are the cutaneous signs of lethal acrodermatitis?

A

Crusty exfoliative lesions of distal extremities, footpads, MC junctions, digits splayed

193
Q

A male castrated dog presented with tail gland hyperplasia. What organ could be affected to cause this change?

A

Adrenal glands

194
Q

A dog presents with unilateral xeromycteria. What is likely to be a concurrent clinical sign?

A

KCS

195
Q

What nerve is affected in parasympathetic nasal hyperkeratosis?

A

Parasympathetic division of the facial nerve (CN 7)

196
Q

What are the histopathologic features of exfoliative dermatitis?

A

CD3+ lymphocytic interface dermatitis
Orthokeratotic hyperkeratosis
Interface mural folliculitis

197
Q

Describe the histopathologic features of SND

A

Parakeratosis (red)
Intra- and intercellular edema with hydropic degeneration (white)
Basal cell hyperplasia (blue)

198
Q

What is the epidermal renewal time in horses?

A

17 days

199
Q

What is the most common keratinization disorder in horses?

A

Cannon keratosis

MK ACVD Exam (18 decks)

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